Sphingosine 1-Phosphate Receptor Subtype 1 as a Therapeutic Target for Brain Trauma

Journal of Neurotrauma
Salvatore CuzzocreaDaniela Salvemini

Abstract

Traumatic brain injury (TBI) provokes secondary pathological mechanisms, including ischemic and inflammatory processes. The new research in sphingosine 1-phosphate (S1P) receptor modulators has opened the door for an effective mechanism of reducing central nervous system (CNS) inflammatory lesion activity. Thus, the aim of this study was to characterize the immunomodulatory effect of the functional S1PR1 antagonist, siponimod, in phase III clinical trials for autoimmune disorders and of the competitive sphingosine 1-phosphate receptor subtype 1 (S1PR1) antagonist, TASP0277308, in pre-clinical development in an in vivo model of TBI in mice. We used the well-characterized model of TBI caused by controlled cortical impact. Mice were injected intraperitoneally with siponimod or TASP0277308 (1 mg/kg) at 1 and 4 h post-trauma. Our results demonstrated that these agents exerted significant beneficial effects on TBI pre-clinical scores in term of anti-inflammatory and immunomodulatory effects, in particular, attenuation of astrocytes and microglia activation, cytokines release, and rescue of the reduction of adhesion molecules (i.e., occludin and zonula occludens-1). Moreover, these compounds were able to decrease T-cell activation vis...Continue Reading

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Citations

Apr 16, 2020·Cell Communication and Signaling : CCS·Yunxiang ZhouJianmin Zhang
Apr 23, 2019·Stroke; a Journal of Cerebral Circulation·Antje VogelgesangJuliane Schulze
Sep 12, 2020·Neuromolecular Medicine·Bhakta Prasad Gaire, Ji Woong Choi
Jul 11, 2021·Journal of Cellular and Molecular Medicine·Michela CampoloIrene Paterniti

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Methods Mentioned

BETA
light microscopy
electrophoresis

Software Mentioned

Axio Vision
ImageJ
Optilab
ImageLab
Image Quant TL
Adobe Photoshop

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